Radical tx and fractionation Flashcards
Radical fractionation for cervix? And indications?
45 in 25 over 5 weeks, 1.8 Gy per fraction (EMBRACE protocol)
Weekly cisplatin 40 mg/m2
Simultaneous integrated boost (SIB) to involved nodes - 10-15Gy (deliver 2.2-2.4Gy/#). 55Gy to pelvic LNs, 57.5-60Gy to extra-pelvic LNs.
Brachytherapy with uterine/vaginal applicator. Pulsed dose rate (PDR) 17Gy x2# given overnight. High dose rate (HDR) 7Gy x 4# (shorter delivery time)
Concurrent chemotherapy adds ~5% OS benefit
Brachytherapy adds ~30% OS benefit
Indications: anything IB III and above (>4cm). Trial comparing surgery to chemorad + brachy found equipoise but more toxicity with adjuvant xrt, so now chemorad is standard.
Neoadjuvant treatment for Oesophageal SCC?
CROSS protocol (2012): Oesophagus/GOJ patients with resectable tumours.
Pre-operative CRT 41.4Gy/23# + weekly carboplatin (AUC 2) and paclitaxel 50mg/m2 vs no pre-op CRT. 75% adenocarcinoma; 23% SCC.
Path CR 29%. Median OS 49.4 vs. 24m.
followed by oesophagectomy
Neoadjuvant treatment for oesophageal adenocarcinoma?
ESOPEC-2 (2024): FLOT better than CROSS chemoRT in adenos. Contentious (CROSS control group did worse than historical data. Why?)
FLOT (6 cycles)
5-FU 2600 mg/m2
Oxaliplatin 85 mg/m2
Docetaxel 50 mg/m2
at 55 months, PFS 51.6 vs 35.
Radical treatment for oesophageal cancer?
Radiotherapy alone:
- 55 in 20 fractions / 55 in 16 if <4cm (10% cure rate)
Chemorad:
Total disease (primary and involved nodes ≤13cm; primary ≤10cm; <3cm gastric extension; PS 0-1.
4x Cisplatin/capecitabine. Cisplatin 60mg/m2 D1 and capecitabine 625mg/m2 bd (D1-21) + 50Gy/25# with C3+C4. cure rate roughly 30% at 3 years.
if unfit for cis/cape, weekly carboplatin (AUC 2) and paclitaxel 50mg/m2 + 50Gy/25#
Adjuvant fractionation for low risk endometrial cancer?
Low: FIGO IA, G1-2, endometrioid, LVSI negative or focal. FIGO I-II POLEmut
Consider omitting radiotherapy
Adjuvant treatment for intermediate risk endometrial cancer?
Intermediate: FIGO IA, G3 endometrioid, LVSI negative OR focal;
FIGO IB, G1-2, endometrioid, LVSI negative or focal.
HDR: 21 Gy at 5 mm in 3 fractions over 2–3 weeks, vaginal vault brachytherapy.
Adjuvant intermediate-risk - vaginal vault brachytherapy (VBT) 21Gy/3# given weekly, reduces risk of vaginal recurrence. PORTEC-2 compared VBT and EBRT. 10yr vaginal recurrence 3.4% vs. 2.4%, 10yr pelvic recurrence 6.3% vs. 0.9%. 10yr OS 69.5% vs. 67.6%. Long term late toxicity due to EBRT is significant. Urinary incontinence, diarrhoea, faecal leakage.
Adjuvant treatment for intermediate-high risk endometrial cancer?
Intermediate-high:
FIGO I endometrioid + substantial LVSI (regardless of grade/invasion depth)
FIGO IB G3 regardless of LVSI status; FIGO II endometrioid.
Adjuvant high-intermediate risk - EBRT 46Gy/23# +/- VBT 8Gy/2# weekly (particularly if no nodal staging, extensive LVSI, FIGO II). VBT alone an option if node negative surgically.
Adjuvant treatment for high risk endometrial cancer?
High: any p53, any non-endometroid
FIGO III/IVA no residual disease
FIGO I-IVa non-endometrioid no residual disease
FIGO I-IVA p53mut no residual disease
PORTEC-3 (2019): covered patients with ‘high risk features’ but no Grade IV
FIGO I G3 + deep myometrial invasion or LVI; FIGO II-III OR FIGO I-III with serous/clear cell histology.
RT alone (48.6Gy/27# vs. 48.6Gy/27# + 2 cycles concurrent cisplatin 50mg/m2 then 4x carboplatin AUC 5/paclitaxel 175mg/m2 3 weekly.
5 year OS 81.4% CRT versus 76.1% RT alone.
Similar trial: 6x carbo/taxol vs portec 3
GOG-258 (2019): FIGO III/IV. CRT (45Gy/25# + 50mg/m2 cisplatin week 1/4) then 4x carbo AUC 5-6/paclitaxel 175mg/m2 versus 6x chemotherapy alone. 5yr RFS 59% versus 58%. Pelvic/para-aortic nodal recurrence at 5 years 11% CRT versus 20% chemotherapy only.
Found fewer distant mets but more local recurrence
Management of metastatic / advanced endometrial ca?
dependent on MMR status
pMMR: 1st + 2nd line Carbo/Taxol and Len/Pem. Then either weekly paclitaxel or caelyx or rechallenge platinum / carbo/caelyx
dMMR: 1st line: Dostarlimab + Carbo/Taxol, or Len/Pem. 2nd line: Dostarlimab, or Pembro, or Len/Pem (whichever hasn’t been used yet.). 3rd line: Carbo/Caelyx, Caelyx, weekly paclitaxel, or Carbo/Taxol (if not yet used in metastatic/advanced setting).
management of metastatic cervical ca?
CPS score dependent. if CPS > 1, pembro + carbo/taxol +/- bevacizumab
Pembro: Keynote 526
First line: Pembro (If CPS >1) + paclitaxel 175mg/m2 + carboplatin AUC5 (consider 6 if GFR>60) 3 weekly x6 + bevacizumab 15mg/kg 3 weekly (no maintenance). Don’t give bevacizumab if bowel obstruction. In trial comparing chemo regimens , carbo/taxol had the highest response rate (29%, PFS 5.8 months, OS 12.8 months).
SABR criteria for HCC?
5 fractions, aim 50Gy max 6 cm
Child Pugh A-B
90% local control rate at one year
Spare 70ccs of liver to allow regeneration
Use a belt around abdomen to reduce inter-fraction movement
2 year OS 80%
Management of vaginal cancers? (and indications)
Surgery - Stage 1, particularly <2cm and upper vagina (resection with preservation of anatomy is more feasible).
Radical hysterectomy; upper vaginectomy; bilateral pelvic lymph node dissection.
5yr survival 77%.
Limited evidence behind XRT given rarity
Aim EQD2 70-80 Gy (lower vagina less tolerant)
45 in 25 fractions (cisplatin 40 mg/m2 confers survival advantage), FOLLOWED BY HDR brachy:
- Upper vagina 24 in 4
- Lower vagina 20 in 5 (lower vagina less tolerant of high doses)
Stage III survival 66% at 5 years
Stage IV survival 25% at 5 years
Treatment for early ovarian cancer?
Full staging involves surgeons with visualisation + washings of the peritoneal cavity
Fertility-sparing: USO (Stage I disease)
Stage IIA, III, IIIB: Standard TAH & BSO + resection of peritoneal deposits + resection of involved nodes
If ++++ ascites or peritoneal disease, consider chemo first after MDT discussion followed by surgery after 3x cycles
Adjuvant indications for ovarian ca SACT + which treatment?
Single agent carbo 6x (AUC 5-6) if not fit for doublet
Carbo/taxol (AUC 5/6 and 175 mg/m2) 3x
IC and above, 6x cycles
TO BE COMPLETED with details of HRD + maintenance etc etc
Management of Ta/T1 bladder cancer? (NMIBC)
Ta: basement membrane
T1: lamina propria (not yet in muscularis propria)
TURBT with intravescical chemotherapy (mmc/doxorubicin/epirubicin) and follow up Intravescical chemotherapy based on risk factor
Very high risk disease should be offered cystectomy
T1: high risk of recurrence in 5 years (42% in 5 years).
Management of MIBC? (T2-T4a). Any alternatives to surgery?
Cystectomy at a centre that does >10 a year, needs lymph node dissection > on its own, 5 year survival is 50%
Therefore, rationale exists for neoadjuvant treatment (8% OS benefit at 5 years). Options are:
Cis/Gem OR dd-MVAC (methotrexate, vinblastine, doxorubicin and cisplatin)
Neoadjuvant chemo 3-4 cycles:
Cisplatin 70mg/m2 D1; Gemcitabine 1000mg/m2 D1/D8 (21 day cycle) x3-4 neoadjuvant with interim CT.
MVAC - methotrexate, vinblastine, doxorubicin, cisplatin. Organ confined response <ypT3 N0 77% vs 63% gemcis. PFS 64% vs 56% 3 years
GETUG/AFU V05 VESPER trial ASCO 2023 OS at 5 years (ddMVAC vs cis-gem in the neoadjuvant/adjuvant setting) was improved in the dd-MVAC arm 64% vs 56% as was also disease-specific survival 5-year rate: 72% vs 59%. dd MVAC more toxic and only 60% of patients completed 6 cycles as planned compared to >80% completed all 4 cycles of Gem Cis as planned.
ESSENTIALLY: dd-MVAC leads to better PFS and OS, but much more toxicity and reduced completion
Median age of patients in trial was 63, median real age of bladder ca patients is 63
NO role for carboplatin here (inferior in trials)
NO role for neoadjuvant radiotherapy (++ local control but no OS benefit)
IO: Adjuvant nivolumab 240 mg 4 weekly IV in T3+/N+/ residual disease post-T2 (Checkmate 274, OS 65 vs 58% at 3 years) even higher in PD-L1 >1%
Alternative:
55Gy/20# OR 64Gy/32# (organ preservation) following TURBT (referred to as trimodality treatment).
MMC 12mg/m2 D1; 5-FU 500mg/m2 D1-5, D16-20)
Relative CI: poor bladder function; extensive CIS; hydronephrosis
How do you treat patients with MIBC who decline cystectomy? any contraindications?
55Gy/20# OR 64Gy/32# (organ preservation) following TURBT (referred to as trimodality treatment).
with weekly gemcitabine 100 mg/m2
Relative CI:
poor bladder function
extensive CIS
hydronephrosis
BCON (2010): T2-4a N0 M0 MIBC. RT (20# OR 32#) +/- CON. 3yr OS 54% vs. 46%. 3yr RFS 54% vs 43%.
Definition and management of low risk prostate cancer?
Low risk: T2a and below (<50% of 1 lobe) / Gleason 3+3 and below / PSA =<10
Active surveillance vs treatment: ProtecT trial. Similar outcomes with surveillance vs RP or EBRT upfront at 15 years, more progression but no OS benefit.
Low risk > Offer to men with Gleason 6 (3+3) as first approach. Can consider for Gleason 7 (3+4), MRI T stage ≤2; Bx result matching MRI; PSAD (density)
Definition of intermediate risk prostate ca + management?
T2 b but not T3 / PSA 10-20 / Gleason 7
Radical prostatectomy without ADT
EBRT 60 Gy in to 20 to prostate, 6 months of ADT overall neoadjuvant + during treatment
Brachy can be used
PACE-A suggests SABR 5 fractions is superior to RP
Management of high risk prostate cancer? (And definition)
PSA > 20 / T3 and above / Gleason >= 8
RP
EBRT 60 Gy in 20 with 47 Gy to nodes (elective dose). 6 months of neoadjuvant ADT followed by 2 years in total adjuvant ADT.
Node positive? RP vs radiotherapy to the prostate, 60 Gy in 20 + prophylactic nodal irradiation (47 Gy to nodes, even if macroscopically involved. Nodal boost is controversial).
2 years of Abiraterone adjuvantly if 2 of 3 high risk features (T2c or above, Gleason >7, PSA >20) not NICE approved
Definition of biochemical recurrence post-RP? How do you treat it?
Biochemical recurrence is defined as 3 consecutive rises on a supersensitive assay that can detect >0.1 (therefore 4 readings) OR 2 consecutive rises on an assay that can pick up >0.2
Treat with 55 Gy in 20 to the prostate bed, EBRT, followed by 1 year of adjuvant hormones.
Neoadjuvant treatment in penile cancer?
Poor quality evidence available due to rarity
Neoadjuvant TIP in >T2/T3 OR >N2 disease, 4 cycles (TIP: paclitaxel, ifosfamide and cisplatin )
rescan after 3
Followed by surgery which should include SLNB/inguinofemoral dissection based on nodal stage
Adjuvant treatment in penile cancer?
can give adjuvant TIP (again evidence is weak in this disease group)
TIP: paclitaxel, ifosfamide and cisplatin
Indications for adjuvant SACT in melanoma?
IIB/IIC (T2b - T4, N0): adjuvant pembro (not approved by NICE)
Stage III (anything nodal):
Nivolumab 240 mg 4 weekly OR 1 year
Pembro 200 mg 4 weekly 1 year
BRAF+? Could also consider dab/tram (150 mg/2mg) 1 year
IV (resected): Nivolumab
Indications for adjuvant RT in Melanoma?
No evidence of OS/DFS benefit but can give if local control is important and is inoperable / R1 resection of mets.
48 in 20. Reduces in-field recurrence
Surgical margins required in melanoma?
T1 (<1mm): 0.5-1cm
T2 (1-2 mm): 1-2 cm
T3/4 (>2mm): 2 cm
T1b and above (<1mm but with ulceration): needs a SLNBx
Curative treatment for cSCC?
Surgery, likely WLE
Then, triage into low/middle/high risk
Low: pT1 (<4mm), no nodes, not beyond dermis, not immunocompromised, clear margins (>1mm)
High: T2 (4-6mm), T1 with involved margins, beyond subcut fat, recurrent, PNI, immuncompromised)
Very high risk: T2 with involved margins, T3 disease (>6mm), PNI, immunocompromised
THEN:
consider further surgery or MMS/adjuvant XRT if high risk
if nodes, will need nodal dissection
Curative doses of XRT if ineligible/declined surgery: 18 in 1 (<3cm field), 35 in 5 (<4cm), or 55 in 20
How do you treat DTC (Differentiated thyroid cancer)?
Thyroidectomy if Thy3 and above (goes up to thy5)
T1 (<1cm), observe
T3 / N1 (>4cm), offer radioiodine ablation
T2, 1.1 GBq
T3/N1, 3.5 GBq
Following this, DRS (dynamic risk stratification) for further TSH suppression
Low risk: stimulated Tg<1ng/ml; neck US negative
Intermediate risk: stimulated Tg<10ng/ml, US neck indeterminate
High risk: stimulated Tg>10ng/ml, US neck abnormal
DRS low: TSH 0.2-2
DRS intermediate: TSH 0.1-0.5
DRS high: TSH <0.1
